Cannabidiol restores hematopoietic stem cell stemness in mouse through Atf2-Lrp6 axis after acute irradiation

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“Bone marrow serves as the residence of hematopoietic stem cells and is recognized as one of the most radiosensitive tissues. Exposure to acute radiation leads to severe damage to bone marrow hematopoiesis which can be fatal, while few clinically applicable medication or specific therapeutic targets have been discovered.

In this study, we found that the administration of cannabidiol significantly enhanced individual survival and restored the reconstitution capacity of bone marrow hematopoietic stem cells within 14 days after irradiation.

Single-cell RNA sequencing analysis demonstrated that the expression levels of genes associated with stemness along with Wnt and BMP signaling pathways were restored by the cannabidiol treatment through the upregulation of Atf2, a transcription factor possessing multifunctional properties. Atf2 upregulation induced by cannabidiol treatment potentially upregulated the expression of Lrp6 to improve the stemness of hematopoietic stem cells. Further functional experiments validated the crucial role of Atf2 in regulating multilineage differentiation potential of bone marrow hematopoietic stem and progenitor cells.

Overall, our findings provide evidence for a promising radioprotective function of cannabidiol and Atf2 as a candidate therapeutic target for acute radiation-induced hematopoietic injury, thereby paving the way for future research in the field.”

https://pubmed.ncbi.nlm.nih.gov/39949985/

“Cannabidiol (CBD) is the primary non-psychoactive chemical from Cannabis Sativa and an important component of hemp seed, a traditional Chinese medicine with a long history of application. Based on its multiple function, CBD has been investigated in fields of nervous system diseases, analgesic therapy, aging, anti-tumor therapy, and so on.2 In this study, we first assessed the potential role of CBD in preventing and treating acute irradiation-induced hematopoietic injury in bone marrow. Using single-cell RNA sequencing and functional assay, we dissected molecular alterations and potential mediator under CBD-treatment which led to the facilitated recovery of the HSC function. Collectively, this work strongly supports the therapeutic application of CBD in irradiation-induced bone marrow hematopoietic injury and highlights Atf2 as a promising therapeutic target herein.”

https://onlinelibrary.wiley.com/doi/10.1002/mco2.70092

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